Sofosbuvir/velpatasvir is an NS5A protein inhibitor/NS5B polymerase inhibitor.
The package insert for Epclusa, the brand name form of sofosbuvir/velpatasvir, recommends one dosing regimen for genotypes 1-6 in patients who are treatment naïve and who do not have cirrhosis or who have compensated cirrhosis.92
However, the AASLD/ISDA algorithm states that if the patient has genotype 3, drug resistance testing should be done.26 If drug resistance testing reveals that the patient has a specific hepatitis C genetic polymorphism, the Y93H polymorphism, a lower SVR may occur, and the AASLD/ISDA recommends that the patient should be treated with sofosbuvir/velpatasvir and weight-based ribavirin or with another drug, e.g., sofosbuvir/velpatasvir/voxilaprevir.26,93,94
Dosing: Once tablet, once a day, for 12 weeks.92
Dosing/geriatric: No dosing adjustments needed.92
Hepatic impairment: Patients who have a mild, moderate, or severe hepatic impairment, Child-Pugh A, B, or C, no dosing adjustment needed.92
Renal impairment: Patients who have mild, moderate, or severe renal impairment, including patients who have ESRD and require hemodialysis, no dosing adjustments needed.92
Contraindications: Epclusa is contraindicated in patients for whom ribavirin is contraindicated.92
US Boxed Warning: Hepatitis B virus reactivation has been reported in hepatitis C and hepatitis B coinfected patients who were undergoing or had completed treatment with hepatitis C direct-acting antivirals, and who were not receiving hepatitis B antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death.92
Warnings and precautions: Concurrent use of sofosbuvir/velpatasvir and amiodarone can cause serious, symptomatic bradycardia. This is especially likely if the patient is also taking a beta-blocker or if she/he has cardiac disease and/or advanced liver disease.92
P-glycoprotein (P-GP) is a transport protein, and one of its primary functions is to move xenobiotics out of cells. P-glycoprotein inducing drugs like carbamazepine and phenytoin can lower the plasma level of sofosbuvir/velpatasvir and reduce its therapeutic effectiveness.92,93 Drugs that are moderate to strong inducers of CYP2B6, CYP2C8, and CYP3A4 can have this effect, as well.92
Adverse effects: Adverse effects occurring in > 5% of patients are asthenia (lack of energy, weakness), fatigue, headache, insomnia, and nausea.91
Drug interactions: The Lexicomp® Drug Interactions database lists 93 drug-drug interactions involving sofosbuvir/velpatasvir, and many involve commonly used medications like anti-diabetic medications, e.g., glipizide and metformin, and warfarin.95
Drug-drug interactions can be checked by using the University of Liverpool, drug interaction checker.26 The website address is www.hep-druginteractions.org/checker. The AASLD/ISDA website has drug-drug interaction information, as well.
Monitoring: If there are no signs and symptoms of liver damage, there is no need to do laboratory testing during the treatment.
Twelve weeks or later, after the last dose, obtain a quantitative measurement of hepatitis C RNA and do a hepatic function panel. If SVR has been attained and the AST and ALT are normal, no further treatment or follow-up is needed.26
If an SVR has been attained, but the AST and ALT are elevated, the patient should be assessed for other causes of liver damage.26
If an SVR has not been attained, the patient should be referred to a specialist.26
Treatment failure will be discussed later in the module.
During clinical trials, the SVR for all patients, with or without compensated cirrhosis, genotypes 1,2, 4,5, and 6, was 99%.9